Ethyl cellulose graft copolymers with block and hetero side chains, ethyl cellulose graft [polystyrene-b-poly(ethylene glycol)] [EC-g-(PS-b-PEG)] and ethyl cellulose graft polystyrene and polyethylene glycol [EC-g-(PS-PEG )] were synthesized by atomic transfer radical polymerization (ATRP) and alkyne-azide "click" reactions and "one-pot" ATRP and "click" reactions, respectively. For the synthesis of EC-g-(PS-b-PEG), the macroinitiator for ATRP was first synthesized via the esterification of hydroxyl groups of EC with 2-bromoisobutyryl bromide to result ethyl cellulose 2-bromoisobutyryl ester (EC-Br). The degree of substitution of bromide groups, which determined the graft density, can be tailored by varying the feeding ratios of the hydroxyl groups to 2-bromoisobutyryl bromide. Then ATRP was carried out for preparing EC-g-PS-Br with well-defined length of PS chains. The EC-g-PS-Br copolymers were then converted to EC-g-PS-N3 and then reacted with end alkyne-functionalized PEG via click to result in EC-g-(PS-b-PEG). The EC-g-(PS-PEG) copolymers were synthesized by converting bromide groups of EC-Br to azide groups (EC-Br-N3) and then by one-pot ATRP and "click" reactions. The resultant graft copolymers were characterized by FTIR and 1H NMR. The results indicate the success of the synthetic procedure of the cellulose graft copolymers with block and hetero side chains.